SUMMARY: OVERALL - Center for Native Environmental Health Research Equity Nearly half of the Native American population of the United States lives in 13 western states in proximity of an estimated 161,000 abandoned hardrock mines, with more than 4,000 being abandoned uranium mines. Because of their reliance on natural resources to maintain traditional diets, lifestyles, customs and languages, these tribal communities have direct and frequent contact with metal mixtures from abandoned mine sites, creating exposures through multiple pathways including inhalation, drinking water, and ingestion of foods either directly or indirectly contaminated by migration of the wastes. Exacerbating these exposures are disparities in infrastructure, including services like safe drinking water and solid waste management. Lack of effective solid- waste management resulted historically in burning and open dumping of solid waste, but with the ever- increasing amounts of plastic entering the waste stream, the low-temperature, incomplete combustion of this process, and the environmental degradation through weathering, our tribal partners are increasingly concerned about the emissions of toxic degradation products of plastics into their environment. The concerns over how the combined toxicants from these processes and the metals we have already linked to immune dysfunction in these communities have led to this Phase 2 Native EH Equity proposal. We have found metals mixtures result in different exposure profiles across our three partnering indigenous communities: Navajo, Apsalooke, and Cheyenne River Sioux. And while we see commonalities in immune dysfunction across these communities that can contribute to disparities in cancer and other chronic diseases, the metals exposures alone do not account for all of the risk. Therefore, in this Phase 2 Center we will develop an understanding of the emerging additional plastic degradation contaminant profiles, evaluating constituents and distribution of microplastics and other degradation products, along with emissions from extractive industries that could add to these classes of chemicals, in both stationary and mobile exposure assessments. We will monitor grazing patterns of livestock and their resulting exposures through air and consumption of plants and water, as well as stationary in-home and mobile monitoring on people during their normal activities to evaluate exposure components and pathways contributing the greatest risk with the ultimate goal of developing mitigation strategies at individual and tribal levels to inform decisions and policies to reduce the risks linked to increasing cancer and other chronic disease disparities in these communities. The resulting fine-scale predictive models, ground-truthed through monitoring, and the integration of multiple exposure streams will provide a resource to not only inform policy, but aid clinicians in identifying early risks to develop prevention strategies as well.